Ann Christine “Christie” Bell was born in Mt. Pleasant, Iowa, in 1950. In 1972, she earned a BA in English from Kirkland College in Clinton, New York. While in college, Bell met Tom Vilsack, a student at nearby Hamilton College. The couple married in 1973, and had two sons, Jess and Doug. After Tom Vilsack received his JD from Albany University in 1975, Tom and Christie moved to Mt. Pleasant, where Christie Vilsack taught middle school and high school language arts and journalism. She later taught English and journalism as an adjunct faculty member at Iowa Wesleyan College. Vilsack earned a master's degree in journalism from the University of Iowa in 1992 and worked as a feature writer and columnist for the Mt. Pleasant News. She developed the "Main Street" column for the newspaper, which she wrote for six years. During this period, Tom Vilsack practiced law with Christie’s father and brother and, in 1987, was elected mayor of Mt. Pleasant. In 1992, he campaigned for and won a seat in the Iowa Senate. Vilsack became First Lady of Iowa after Tom Vilsack's election as Iowa governor in 1999; that same year, she sponsored the Young Women’s Health Conference featuring Second Lady Tipper Gore. Christie Vilsack pursued an active advocacy agenda as First Lady and was particularly involved in promoting literacy in her non-profit Stories 2000. Between 2000 and 2006, Vilsack raised funds to give a book about Iowa each year to 40,000 kindergarteners and started one of the first online book clubs for middle school students. She visited over 500 Iowa libraries to discuss the social and economic benefits libraries bring to communities and to promote family storytelling. She created the Glass Apple award to highlight the work of Iowa’s teacher-librarians and served on the national board of Reach Out and Read.

In 2007, Christie Vilsack launched the Vilsack Foundation to continue her work promoting literacy, libraries, and storytelling. As president of the Foundation, Vilsack partnered with the Verizon Foundation and the National Center for Family Literacy to create the national Tech Savvy Award, which recognized media and information literacy programs around the country that encourage parents to learn the technologies their children use. She also began serving as executive director of The Iowa Initiative, a five-year research program aimed at reducing the high rate of unintended pregnancies among women ages 18-30 in Iowa. This program became well-known for its promotional campaign “Until You’re Ready, Avoid the Stork,” which featured a mascot in a stork costume who appeared in TV ads, billboards and at public events such as athletic events and county fairs. Vilsack has maintained an independent political identity throughout her life. In 1999, Al Gore sought Vilsack’s support for his 2000 bid for the presidency. In 2004, she endorsed John Karry before the Iowa Caucus and attended the Democratic National Convention as a delegate and a speaker. During 2006 and 2007 she traveled the country meeting prominent Democrats in key states to prepare for her husband’s entry into the 2008 presidential election. After her husband withdrew his candidacy, both Vilsacks endorsed Senator Hillary Rodham Clinton.

In July of 2011, Vilsack announced her candidacy as a Democrat against Steve King to represent Iowa's 4th district in the U.S. House and lost the election in November 2012. In 2013, she began working for the U.S. Agency for International Development (USAID) as the Senior Advisor for International Education, a role she remained in until 2016. In this position she traveled to developing countries, to colleges and universities and educated over 70 members of Congress about USAID’s work to teach millions of children to read, educate girls, especially in countries in crisis, and help governments train young adults for jobs. At this time, she also served on the Library of Congress Literacy Awards committee.

From 2017-2021 she worked for the Chancellor of Colorado State University to help create the university’s K-12 educational programming on issues related to water, food, and animal health at CSU’s new Spur campus at the National Western Center. Since 2025, Vilsack has been writing a self-titled Substack column focused on sharing the stories of Iowans "living close to the land who believe in community and the public good."

The Vilsacks currently live next to their son Jess, his wife Kate and their three children, Jake, Caroline and Amelia, who attend Van Meter Community Schools. Their granddaughter Ella died in 2016. They also spend time in Colorado with son Doug, daughter-in-law Janet Lopez and their children Cassin and Ana.